Most cells of the human body have structures known as cilia, which are critical for the cell’s ability to sense its external environment. It has been suggested that there is a potential link between these structures and cancer development. In fact, 70-100% of sarcomas show loss of these primary cilia and the structures that give rise to cilia: centrioles. However, the role of cilia, and the genes associated with cilia formation in the development of sarcoma, is as yet unknown.
Dr Tanos has previously studied a protein involved with cilia known as TTBK2. This protein has been found to be mutated in a number of cancers, and so may also be involved in cancer development. Preliminary data shows that cells with a TTBK2 mutation are unable to grow cilia. This is a new, unexplored area but a hypothesis is that the presence of cilia could impose a barrier to sarcoma development.
This project will examine the role of TTBK2 in a sarcoma model by removing the TTBK2 gene and seeing how this affects cancer development. Findings will then be validated in a patient-derived cell line. The team will also analyse patient samples to see whether the presence or absence of TTBK2, and another protein, can be used as a marker for changes in the cilia in sarcoma.
This research hopes to increase our knowledge of sarcoma at the most fundamental level, and to provide tools for the discovery of new ways to treat and cure sarcomas.
- Tanos, B. et al. Novel cilia function in acquired resistance to kinase inhibitors. Poster presented at Sarcoma UK’s Sarcoma Research Symposium (Basic Science). September, 2016. London, UK.